Serena Boccella1, Elisabetta Panza2, Liliana Lista3, Carmela Belardo1, Angela Ianaro2, Mario De Rosa1, Vito de Novellis4, Vincenzo Pavone5. 1. Department of Experimental Medicine, Università degli Studi della Campania, Naples, Italy. 2. Department of Pharmacy, University of Naples Federico II, Naples, Italy. 3. Department of Chemical Sciences, University of Naples Federico II, Naples, Italy. 4. Department of Experimental Medicine, Università degli Studi della Campania, Naples, Italy. vito.denovellis@unicampania.it. 5. Department of Chemical Sciences, University of Naples Federico II, Naples, Italy. vipavone@unina.it.
Abstract
BACKGROUND: Inflammation plays a key role in the pathogenesis of several chronic diseases. The urokinase plasminogen activator receptor (uPAR) exerts a plethora of functions in both physiological and pathological processes, including inflammation. OBJECTIVE AND DESIGN: In this study, we evaluated the anti-inflammatory effect of a novel peptide ligand of uPAR, UPARANT, in different animal models of inflammation. SUBJECTS AND TREATMENT: Rats and mice were divided in different groups (n = 5) for single or repeated administration of vehicle (9% DMSO in 0.9% NaCl), UPARANT (6, 12 and 24 mg/kg) or dexamethasone (2 mg/kg). Animals were subjected to carrageenan-induced paw oedema or zymosan-induced peritonitis. METHODS: UPARANT effects were tested on: (1) the carrageenan-induced paw oedema volume, (2) the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the nitrite/nitrate (NOx) levels in the paw exudates, (3) cells recruitment into the peritoneal cavity after zymosan injection and (4) NOx levels in the peritoneal lavage. RESULTS: UPARANT (12 and 24 mg/kg) reduced inflammation in both experimental paradigms. Analysis of pro-inflammatory enzymes revealed that administration of UPARANT reduced iNOS, COX2 and NO over-production. CONCLUSIONS: Our study provides a solid evidence that UPARANT reduces the severity of inflammation in diverse animal models, thus representing a novel anti-inflammatory drug with potential advantages with respect to the typical steroidal agents.
BACKGROUND: Inflammation plays a key role in the pathogenesis of several chronic diseases. The urokinase plasminogen activator receptor (uPAR) exerts a plethora of functions in both physiological and pathological processes, including inflammation. OBJECTIVE AND DESIGN: In this study, we evaluated the anti-inflammatory effect of a novel peptide ligand of uPAR, UPARANT, in different animal models of inflammation. SUBJECTS AND TREATMENT: Rats and mice were divided in different groups (n = 5) for single or repeated administration of vehicle (9% DMSO in 0.9% NaCl), UPARANT (6, 12 and 24 mg/kg) or dexamethasone (2 mg/kg). Animals were subjected to carrageenan-induced paw oedema or zymosan-induced peritonitis. METHODS: UPARANT effects were tested on: (1) the carrageenan-induced paw oedema volume, (2) the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the nitrite/nitrate (NOx) levels in the paw exudates, (3) cells recruitment into the peritoneal cavity after zymosan injection and (4) NOx levels in the peritoneal lavage. RESULTS: UPARANT (12 and 24 mg/kg) reduced inflammation in both experimental paradigms. Analysis of pro-inflammatory enzymes revealed that administration of UPARANT reduced iNOS, COX2 and NO over-production. CONCLUSIONS: Our study provides a solid evidence that UPARANT reduces the severity of inflammation in diverse animal models, thus representing a novel anti-inflammatory drug with potential advantages with respect to the typical steroidal agents.
Authors: Filippo Locri; Noemi A Pesce; Monica Aronsson; Maurizio Cammalleri; Mario De Rosa; Vincenzo Pavone; Paola Bagnoli; Anders Kvanta; Massimo Dal Monte; Helder André Journal: J Mol Med (Berl) Date: 2020-09-17 Impact factor: 4.599